This paper presents a system for mechanically characterizing single cells using automated micropipette aspiration. Using vision-based control and position control, the system controls a micromanipulator, a motorized translation stage, and a custom-built pressure system to position a micropipette (4 μm opening) to approach a cell, form a seal, and aspirate the cell into the micropipette for quantifying the cell’s elastic and viscoelastic parameters as well as viscosity. Image processing algorithms were developed to provide controllers with real-time visual feedback and to accurately measure cell deformation behavior on line. Experiments on both solid-like and liquid-like cells demonstrated that the system is capable of efficiently performing single-cell micropipette aspiration and has low operator skill requirements.
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An, S. S., B. Fabry, X. Trepat, N. Wang, and J. J. Fredberg. Do biophysical properties of the airway smooth muscle in culture predict airway hyperresponsiveness? Am. J. Respir. Cell Mol. Biol. 35(1):55–64, 2006.
Bao, G., and S. Suresh. Cell and molecular mechanics of biological materials. Nat. Mater. 2(11):715–725, 2003.
Cross, S. E., Y.-S. Jin, J. Rao, and J. K. Gimzewski. Nanomechanical analysis of cells from cancer patients. Nat. Nanotechnol. 2(12):780–783, 2007.
Dougherty, E. R., and R. A. Lotufo. Hands-on Morphological Image Processing. Bellingham, WA: SPIE, 2003.
Evans, E., and A. Yeung. Apparent viscosity and cortical tension of blood granulocytes determined by micropipet aspiration. Biophys. J. 56(1):151–160, 1989.
Fabry, B., G. Maksym, J. Butler, M. Glogauer, D. Navajas, and J. Fredberg. Scaling the microrheology of living cells. Phys. Rev. Lett. 87(14):1–4, 2001.
Hashimoto, K. A review on vision-based control of robot manipulators. Adv. Robotics 17(10):969–991, 2003.
Haupt, B. J., A. E. Pelling, and M. A. Horton. Integrated confocal and scanning probe microscopy for biomedical research. Sci. World J. 6:1609–1618, 2006.
Heinrich, V., and W. Rawicz. Automated, high-resolution micropipet aspiration reveals new insight into the physical properties of fluid membranes. Langmuir 21(5):1962–1971, 2005.
Hochmuth, R. M. Micropipette aspiration of living cells. J. Biomech. 33(1):15–22, 2000.
Kim, D.-H., P. K. Wong, J. Park, A. Levchenko, and Y. Sun. Microengineered platforms for cell mechanobiology. Annu. Rev. Biomed. Eng. 11:203–233, 2009.
Lee, G. Y. H., and C. T. Lim. Biomechanics approaches to studying human diseases. Trends Biotechnol. 25(3):111–118, 2007.
Leith, D. J., and W. E. Leithead. Survey of gain-scheduling analysis and design. Int. J. Control 73(11):1001–1025, 2000.
Lewis, J. P. Fast normalized cross-correlation. Vis. Interface 10(1):120–123, 1995.
Lim, C. T., E. H. Zhou, A. Li, S. R. K. Vedula, and H. X. Fu. Experimental techniques for single cell and single molecule biomechanics. Mater. Sci. Eng. C 26(8):1278–1288, 2006.
Lim, C. T., E. H. Zhou, and S. T. Quek. Mechanical models for living cells—a review. J. Biomech. 39:195–216, 2006.
Liu, X., Y. Wang, and Y. Sun. Cell contour tracking and data synchronization for real-time, high-accuracy micropipette aspiration. IEEE Trans. Autom. Sci. Eng. 6(3):536–543, 2009.
Lu, Z., C. Moraes, G. Ye, C. A. Simmons, and Y. Sun. Single cell deposition and patterning with a robotic system. PLoS ONE 5(10):e13542, 2010.
Merryman, W. D., P. D. Bieniek, F. Guilak, and M. S. Sacks. Viscoelastic properties of the aortic valve interstitial cell. J. Biomech. Eng. 131:041005, 2009.
Merryman, W. D., I. Youn, H. D. Lukoff, P. M. Krueger, F. Guilak, R. A. Hopkins, and M. S. Sacks. Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis. Am. J. Physiol. Heart Circ. Physiol. 290(1):H224–H231, 2006.
Mills, J. P., L. Qie, M. Dao, C. T. Lim, and S. Suresh. Nonlinear elastic and viscoelastic deformation of the human red blood cell with optical tweezers. Mech. Chem. Biosyst. 1(3):169–180, 2004.
Needham, D., and R. M. Hochmuth. Rapid flow of passive neutrophils into a 4 microns pipet and measurement of cytoplasmic viscosity. J. Biomech. Eng. 112(3):269–276, 1990.
Pravincumar, P., D. L. Bader, and M. M. Knight. Viscoelastic cell mechanics and actin remodelling are dependent on the rate of applied pressure. PLoS ONE 7:e43938, 2012.
Rugh, W. J., and J. S. Shamma. Research on gain scheduling. Automatica 36(10):1401–1425, 2000.
Sato, M., D. P. Theret, L. T. Wheeler, N. Ohshima, and R. M. Nerem. Application of the micropipette technique to the measurement of cultured porcine aortic endothelial cell viscoelastic properties. J. Biomech. Eng. 112(3):263, 1990.
Schreier, R., and G. C. Temes. Understanding Delta–Sigma Data Converters, Vol. 22. Piscataway, NJ: Wiley-IEEE Press, p. 464, 2005.
Shao, J. Y., and R. M. Hochmuth. The resistance to flow of individual human neutrophils in glass capillary tubes with diameters between 4.65 and 7.75 microns. Microcirculation 4(1):61–74, 1997.
Simmons, C. A. Aortic valve mechanics: an emerging role for the endothelium. J. Am. Coll. Cardiol. 53(16):1456–1458, 2009.
Suresh, S. Biomechanics and biophysics of cancer cells. Acta Biomater. 3(4):413–438, 2007.
Theret, D. P., M. J. Levesque, M. Sato, R. M. Nerem, and L. T. Wheeler. The application of a homogeneous half-space model in the analysis of endothelial cell micropipette measurements. J. Biomech. Eng. 110(3):190–199, 1988.
Tsai, M. A., R. S. Frank, and R. E. Waugh. Passive mechanical behavior of human neutrophils: power-law fluid. Biophys. J. 65(5):2078–2088, 1993.
Tsai, M. A., R. E. Waugh, and P. C. Keng. Cell cycle-dependence of HL-60 cell deformability. Biophys. J. 70(4):2023–2029, 1996.
The authors thank John Nguyen for helpful discussions and thank Haijiao Liu and Prof. Craig Simmons for PAVIC cell preparation. The authors acknowledge financial support from the Natural Sciences and Engineering Research Council of Canada and the Canada Research Chairs Program.
Conflict of interest
The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
Associate Editor Scott I Simon oversaw the review of this article.
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Shojaei-Baghini, E., Zheng, Y. & Sun, Y. Automated Micropipette Aspiration of Single Cells. Ann Biomed Eng 41, 1208–1216 (2013) doi:10.1007/s10439-013-0791-9
- Robotic cell manipulation
- Visual servoing
- Biological cell characterization
- Micropipette aspiration
- Mechanical properties